Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort.

BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Gastrointestinal stromal tumors and second primary malignancies: a retrospective monocentric analysis.

In the post-Imatinib era, the median survival of patients diagnosed with GIST has reached almost 5 years. Prolonging GIST-specific survival, GIST patients have an increased incidence of secondary neoplasia. Data on the prognostic impact of second tumors in GIST patients are very poor with few and small retrospective analyses available in the literature. We conducted a retrospective monocentric analysis on 145 patients diagnosed with GIST between April 2001 and October 2018. Kaplan-Meier and Cox hazard methods were used for survival analysis. A total of 154 GIST patients were included and 31 patients of them (21%) were diagnosed with at least one additional malignancy. The most common second tumors associated with GIST were gastrointestinal tumors. GIST patients with additional malignancies showed to have lower size (>5 cm: 35% vs 45%; p=0.75), higher mitotic rate (>5/50 HPFs: 42% vs 29%; p=0.24), higher presence of c-KIT mutation (85% vs 69%), a lower presence of PDGFRα mutation (8% vs 17%; p=0.05) and shorter survival (mOS: 9.6 vs 15.5 years; p=0.30). In conclusion, our study did not find any significant correlation between clinicopathological characteristics and the development of a second tumor in GIST patients. Further analyses and strict follow up protocols are needed in order to early diagnose and promptly treat a second primary tumor in the GIST population.

Molecular characterization of an Italian series of sporadic GISTs.

PURPOSE: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Most (80 %) contain activating mutations in the KIT receptor tyrosine kinase, roughly 10 % in platelet-derived growth factor receptor-alpha (PDGFRA). In a small subset, BRAF mutations are an alternative molecular pathway. GISTs respond well to imatinib, but low response is seen in patients with wild-type KIT or PDGFRA. Resistance has also been reported as a result of mutations in downstream effectors such as BRAF. METHODS: We provide here a molecular characterization of a series of primary GISTs from Italian patients. Of 121 GIST cases diagnosed between 2000 and 2012, 83 were evaluated by PCR amplification and direct sequencing for mutations in KIT exons 8, 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and BRAF exon 15. Eighty-one GISTs also underwent K-RAS testing. RESULTS: Sixty-four GISTs were positive: 55 had mutations in KIT and 9 in PDGFRA; 16 patients were mutation negative. Three samples came from NF1 patients and were KIT- and PDGFRA negative. Overall, we identified six novel mutations in KIT (p.K550_M552delinsL, p.Q556_W557delinsG p.Q556_G575del, p.W557_V559delinsQ p.P573_R588dup, p.G592_K593dup) and one novel mutation in PDGFRA (p.D842_N848delinsVDV), thus contributing to widening the spectrum of known mutations in GIST tumors and confirming the most frequently altered regions underlying GIST development. CONCLUSIONS: Among the 64 KIT- and PDGFRA-positive sporadic patients in our series, no BRAF or KRAS mutations were identified, suggesting that co-occurrence of these mutations is likely to be rare in the northwestern Italian population and not a frequent cause of primary resistance to imatinib in KIT-positive GIST patients.

Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies.

BACKGROUND: asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 µg/m(2) as optimal biological and maximum-tolerated dose, respectively. PATIENTS AND METHODS: Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 µg/m(2) in combination with capecitabine-oxaliplatin (XELOX). RESULTS: Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy. CONCLUSIONS: Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.

First-line single-agent cetuximab in patients with advanced colorectal cancer.

BACKGROUND: The anti-epidermal growth factor receptor (EGFR) antibody cetuximab is active in heavily pretreated patients with metastatic colorectal cancer (mCRC) both in monotherapy and in combination with chemotherapy (CT). This study assesses the antitumor activity of single-agent cetuximab in CT-naive patients. PATIENTS AND METHODS: Phase II clinical trial was used. Patients were EGFR positive by immunohistochemistry and were not candidate for radical surgery, even in the case of substantial tumor shrinkage. Cetuximab was administered weekly. RESULTS: Thirty-nine patients were treated and evaluated. The most common adverse event was skin toxicity (89% any grade; 48% grade 1; 31% grade 2; 10% grade 3). One patient had a complete response and three obtained partial responses (10% overall response rate). Thirteen patients had stable disease (34%). Twenty-two patients experienced progressive disease (56%). Overall median time to progression (TTP) was 2 months, and the responders individual TTP was 12, 9, 9, and 6 months. CONCLUSIONS: Even in chemo-naive patients, cetuximab as single agent is active only in a small fraction of mCRC, similarly to what has been reported for heavily pretreated patients. The extent of benefit when response occurs is, however, such that it is mandatory to intensify the search for the predictive markers of response to cetuximab therapy.

Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab.

In a randomised phase 3 trial, panitumumab significantly improved progression-free survival (PFS) in patients with refractory metastatic colorectal cancer (mCRC). This analysis characterises the association of PFS with CRC symptoms, health-related quality of life (HRQoL), and overall survival (OS). CRC symptoms (NCCN/FACT CRC symptom index, FCSI) and HRQoL (EQ-5D) were assessed for 207 panitumumab patients and 184 best supportive care (BSC) patients who had at least one post-baseline patient-reported outcome (PRO) assessment. Patients alive at week 8 were included in the PRO and OS analyses and categorised by their week 8 progression status as follows: no progressive disease (no PD; best response of at least stable disease) vs progressive disease (PD). Standard imputation methods were used to assign missing values. Significantly more patients were progression free at weeks 8-24 with panitumumab vs BSC. After excluding responders, a significant difference in PFS remained favouring panitumumab (HR=0.63, 95% CI=0.52-0.77; P<0.0001). At week 8, lack of disease progression was associated with significantly and clinically meaningful lower CRC symptomatology for both treatment groups and higher HRQoL for panitumumab patients only. Overall survival favoured no PD patients vs PD patients alive at week 8. Lack of disease progression was associated with better symptom control, HRQoL, and OS.

[Surgical resection of gastrointestinal stromal tumor after treatment with imatinib: clinical case]. / Resezione chirurgica di un tumore stromale gastrointestinale dopo trattamento con imatinib: un caso clinico.

The stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection is the first-line therapy for operable lesions, however for inoperable imatinib is an effective therapy. In this setting a patient has been operated after a remarkable response to imatinib, used as both neoadjuvant and adjuvant. This approach led to a disease-free condition without toxicity and complications.

Life expectancy, comorbidity and quality of life: the treatment equation in the older cancer patients.

With ageing, function preservation and maintenance of quality of life represent a major goal in an increasing proportion of patients. Life expectancy is a function of age, comorbidity, disability and cancer type and stage. Decision-making involves a delicate balance among all these factors, evaluation of treatment related complications of the overall effects of cancer and cancer treatment on the patients' quality of life. Despite several instruments for the assessment of quality of life being validated, none have been calibrated to the special requirements of the older patients. The structured interview administered by a trained clinician represents a standard approach for geriatric research and even for clinical practice because of the frailty of the older population. The combination of this approach with the self-administered questionnaire appears the most effective way to minimise missing data in collecting information for patients unable to complete the form.

Formestane is feasible and effective in elderly breast cancer patients with comorbidity and disability.

Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65-93), with nine patients > 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated - only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.

Cancer in the elderly: assessing patients for fitness.

As aging is highly heterogeneous, the clinical evaluation of the older person with cancer is influenced by several factors including comorbid conditions, disabilities, tumour type and stage. Assessment of comorbidity and disability represent on evolving area of research. Results from geriatrics are now translating in clinical oncology. Instruments for measurement of comorbidity and disability have been evaluated in the older cancer patients with promising results. The use of comprehensive geriatric assessment (CGA) in the older cancer patient represents a major improvement in the oncological practice. CGA is based on standardised interviews and covers areas of physical and psychical dysfunction. Moreover, CGA allows the collections of homogeneous information among different centres and recognition of the frail elderly. A diffuse ageistic prejudice may prevent adequate evaluation and treatment of older individuals. A wide based educational effort may allow a more appropriate management of the older cancer patient.

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin.

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A - vinorelbine 30 mg/m2 i.v. weekly; Arm B - leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 5, q 28 days; Arm C - mitoxantrone 12 mg/m2 i.v. only day 1 + leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 3, q 28 days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3-4 toxicities. Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.

[Malignant phyllodes tumor with liposarcomatous differentiation. Description of a clinical case]. / Tumore filloide maligno con differenziazione liposarcomatosa. Descrizione di un caso clinico.

Sarcoma of the breast are a rare group of neoplasms representing less than 5% of Soft Tissue Sarcomas (STS). Between 1980 and 1995 in the National Institute foe Cancer Research (IST) of Genoa, 2188 patients were submitted to surgery for breast cancer. Seven of them were found to be affected by sarcoma, confirmed by histologic diagnosis. All the patients were between 39 and 87 years-old. Surgical treatments were: wide excision (1 case), total mastectomy (2 cases), radical mastectomy following Halsted (4 cases). A case of a 53 year-old woman with a phyllodes tumor initially transforming in to liposarcoma is reported. The patient was submitted to surgery (total mastectomy) and nowadays is alive and free of disease after 29 months. All authors agree that the treatment for sarcoma of the breast is early and complete surgical excision of the mass. The role of chemotherapy and radiotherapy is still uncertain. Outcome is based on histologic type, degree of differentiation and tumor size.

[Diagnostic protocol of thyroid nodules used in a surgical case series (409 cases)]. / Protocollo diagnostico dei noduli tiroidei utilizzato in una casistica chirurgica (409 casi).

BACKGROUND: The introduction of ultrasonography and fine needle biopsy (FNB) has changed the approach towards thyroid pathology. At the Division of Surgical Oncology of the National Institute for Cancer Research in Genoa we use a complex diagnostic system for the selection of patients affected by thyroid pathologies. Our aim is to analyze this methodology and find the best diagnostic procedure for the individual patient. METHODS: Between January 1982 and June 1997, 2500 patients (pts) were found to be affected by thyroid pathologies. The diagnostic procedures for thyroid pathologies are: physical examination and anamnesis, scintigraphy, ultrasonography, fine needle biopsy, blood dosages, radiography of trachea and aesophagus; some cases require Computerized Tomography of the neck and Magnetic Nuclear Resonance. At the end of the examinations 409 pts underwent surgery; we will be evaluating the diagnostic system of these patients. RESULTS: We found from our data, that the group with the highest incidence of malignant tumors is characterized by a large number of instrumental examinations. In fact, 55/73 pts underwent all the instrumental exams, and in 21.1% a malignant tumor was found. These data are interesting, but more important is that only 409 patients out of 2500 underwent surgery 16.3%. CONCLUSIONS: We believe that one single instrumental examination is not enough to detect the characteristic of a thyroid nodule; the three most important examinations, scintigraphy, ultrasonography and cytology, would make it possible to select those cases which need a surgical approach. We believe that the 20% incidence in these cases can be considered good result, considering that the incidence of malignant tumors in thyroid pathologies is about 5% and that in these cases although the tumors were not malignant, they were operated on for functional or mechanical disorder.

[Precancerous lesions of the oral cavity: review of the literature and an analysis of cases]. / Lesioni precancerose del cavo orale: revisione della letteratura ed analisi di una casistica.

146 patients with precancerous lesions of the oral cavity were observed in our institute between 1988 and 1995. Out of a total of 188 lesions, 110 were single and 36 were multifocal. Histologically 164 lesions were classified as keratosis, 14 as dysplasia, and 10 as lichen ruber planus. 76 patients were treated by cryosurgery, 20 received medical treatment and 3 underwent surgery. Only 47 patients eliminated such risk factors as smoking and alcohol consumption from their daily life-styles. Complete response was 99%, 20.8% and 29.8%, respectively, for cryosurgery, medical treatment and preventive measures. Only 2 patients (1.4%) developed squamous cell carcinoma of the oral cavity. Of these, 1 had had keratosis of the tongue, treated with cryosurgery, while the other had had a medically treated dysplasia of the floor of the mouth. There were 8 precancerous lesion recurrences after cryosurgery and 2 after medical treatment. After cryosurgery 18 new lesions appeared in a site other than the primary site, 4 occurred after medical treatment, 1 after surgery and 2 in patients who had eliminated tobacco and alcohol consumption. Since precancerous lesions constitute a general apparatus disease, a systemic treatment is required which can stimulate cell differentiation and/or suppress the mechanisms inducing carcinogenesis. This may prevent the occurrence of new lesions. For this reason the authors believe that the initial treatment for patients with precancerous lesions should be medical. Loco-regional therapy should be reserved for those cases which do not respond to medical treatment.

[The role of the general practitioner and dentist in the early diagnosis of preneoplastic and neoplastic lesions of the oral cavity]. / Il ruolo del medico generico e dell'odontostomatologo nella diagnosi precoce delle lesioni preneoplastiche e neoplastiche del cavo orale.

Early detection of oral cancer allows for a 90% 5-year survival rate. Unfortunately, nowadays 60% of these tumors are detected in advanced stages with a 5-year survival of about 20%. Therefore, early diagnosis is of the greatest importance. Both the GP and the dentist have a primary role in early diagnosis and are also responsible for informing the population regarding the risk factors in oral cancer. GPs and dentists should systematically check the oral cavity mucous membranes in heavy smokers and/or drinkers above all when over 40. Lesions become suspicious when they persist for more than two weeks after detection. The high-risk pts and suspicious lesions should undergo the following diagnostic procedures: micronucleus test, vital staining, scraping and biopsy for cytological and histological examination. The above mentioned methods will increase the early diagnosis of tumours and improve its prognosis.

Combined craniofacial approach to facial tumours involving the anterior skull base.

The authors report their experience on six male patients and one female patient (age range: 58-76 years, median: 67) with facial tumours involving the anterior skull base, undergoing craniofacial resection between January 1992 and May 1994 at the Division of Surgical Oncology in the Tumor Institute, Genoa. Three patients had squamous carcinoma and adenocarcinoma of the nasal fossa; two patients had squamous carcinoma rT4NO and adenocarcinoma rT4NO1 of the maxillary sinus; one patient had squamous carcinoma of the eyelid, and another had squamous carcinoma of the internal chantus. Four patients had had previous radiotherapy, another underwent pre-operative chemoradiotherapy, and only two patients had not been treated before. A proper craniofacial tumour resection was performed in three patients; one patient had a left maxillectomy with ethmoidectomy and orbital exenteration; one patient underwent maxillectomy, resection of the medial and inferior wall of the orbit, ethmoidectomy, and orbital exenteration; one patient underwent maxillectomy, ethmoidectomy, and mucosectomy of the sphenoidal sinus, and one patient had total ethmoidectomy. As for reconstruction procedures of the anterior skull base, lyophilized dura with galeal pericranial flap was commonly used. A myocutaneous flap transposition (transverse rectus abdominis and latissimus dorsi myocutaneous flap) was used in two patients for the reconstruction of the resected tissues and bones of maxillary and orbital regions. Post-operative complications included intraoperative liquorrhea in one patient; one case of early and serious pneumocephalus; flap necrosis occurred following transposition of latissimus dorsi. Median hospital stay was 34 days. After a median follow-up of 18 months (range: 3 to 34 months) five of seven patients (71.4%) are alive and disease-free at 15, 17, 18, 30 and 34 months from surgery.

Radiation-associated angiosarcoma: diagnostic and therapeutic implications--two case reports and a review of the literature.

BACKGROUND: Angiosarcoma (AS) accounts for 1 to 2% of all soft tissue sarcoma. Both primary and secondary AS may occur, the latter being reported in the upper extremity with lymphedema after extended radical mastectomy for breast cancer (postmastectomy AS) or following radiotherapy of the breast, the thoracic wall, or other sites (radiation-associated AS). The authors report two cases of cutaneous radiation-associated AS and review literature regarding treatment planning and follow-up data to define the most appropriate therapy for cutaneous and noncutaneous radiation-associated AS. METHODS: The clinical records of two patients with radiation-associated AS were analyzed and previously reported cases were reviewed. RESULTS: Case 1: a female age 67 years developed cutaneous AS in the residual breast 27 months after breast-conserving therapy and conventional external beam radiotherapy (EBR). She underwent chemotherapy followed by simple mastectomy and chemotherapy with the same regimen but developed early recurrence that was treated with hyperthermia and EBR, wide excision, and second-line chemotherapy. She died 30 months after primary diagnosis of AS with multiple metastases. Case 2: a male age 59 years developed cutaneous AS in the left groin, 10 years after conservative surgery and EBR for a penile carcinoma. Early recurrence following wide excision was treated with chemotherapy, re-excision, and immunochemotherapy but the patient died 24 months after the primary diagnosis of cutaneous AS with local progression and distant metastases. CONCLUSIONS: The prognosis of radiation-associated AS is dismal, due mostly to its poor differentiation and frequent diagnostic delay. Simple mastectomy is advised for patients with cutaneous AS after breast-conserving surgery with wide tumor-free margins. If primary surgery fails, survival is seriously compromised because adjuvant or palliative treatments are not effective.

[Early stages of laryngeal cancer (I-II stage) and therapeutic options: case report and review of literature]. / Tumori della laringe I-II stadio; opzioni terapeutiche, presentazione di una casistica e revisione della letteratura.

Between 1987 and 1993, 36 patients with early squamous cell carcinoma of the larynx (I-II stage) were treated with radiotherapy, at the National Institute for Cancer Research of Genoa; 25 patients were stage I (5 T1N0 of supraglottic larynx, 15 T1aN0 and 5 T1bN0 of glottic larynx) and 11 patients stage II (7 T2N0 of supraglottic larynx and 4 T2N0 of glottic larynx); there were 32 males (89%) and 4 females (11%), ages ranging from 34 to 83 years (mean age 61 years). The radiotherapy was performed utilizing the X-ray of a 6 MV linear accelerator, with a daily conventional fractionation and a dose of 66-70 Gy/33-35 fr./7 weeks, with co-axial latero-lateral beams including cervical lymph-nodes, except for T1N0 glottic cancer. The median follow-up was 51 months (range 8-84 months). The local control rate of all the patients was 80.5% at 51 months. According to the stage and tumor subsite, it was 80% for stage I a-b of the glottic site, 60% for the stage I of supraglottic site, 91% for stage II of supraglottic and glottic site. Only 6 patients (18%) underwent the salvage surgery and in all the patients the illness was under control. The overall survival rate was 83.3% at 51 months (4 patients died of a second tumor (11%) and 2 from heart disease (5.5%)). The only complication we observed was a glottic edema. The analysis of our results demonstrates that radiotherapy seems to be more appropriate in the T1a-b glottic cancer. These results are in agreement with those obtained by other studies. On the contrary, the results obtained with radiotherapy, in the T2N0 glottic cancer, are not satisfactory, with regard to local control, as those obtained with surgery, but offers best functional results. In most T2N0 tumors, after the failure of radiotherapy, a reconstructive laryngectomy is still possible. We also obtained good results with the supraglottic lesions. The small number of cases we treated does not allow us to achieve final conclusions and other studies are necessary to confirm our results.